The effect of chemical sympathectomy on cardiovascular parameters and the compensatory role of adrenal hormones, the renin-angiotensin system, and cardiovascular sensitivity to vasoconstrictors were studied in spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats. Sympathectomy was induced in 20-week-old rats by daily intraperitoneal guanethidine administration (30 mg/kg b.w.) for 2 weeks. Basal blood pressure (BP), heart rate (HR), and restraint stress-induced cardiovascular changes were measured by radiotelemetry. The BP response to catecholamines was determined in rats with implanted catheters. Sympathectomy decreased BP only transiently, and after 14-day guanethidine treatment, BP returned to basal values in both strains. Sympathectomy permanently lowered HR, improved baroreflex sensitivity, and decreased the low-frequency domain of systolic blood pressure variability (a marker of vascular sympathetic activity). Guanethidine also attenuated the BP and HR responses to restraint stress. On the other hand, the BP response to catecholamines was augmented in sympathectomized rats, and this was not due to the de novo synthesis of vascular adrenergic receptors. Sympathectomy caused adrenal enlargement, enhanced the expression of adrenal catecholamine biosynthetic enzymes, and elevated plasma adrenaline levels in both strains, especially in WKY rats. Guanethidine also increased the plasma levels of aldosterone and corticosterone in WKY rats only. In conclusion, sympathectomy produced a transient decrease in BP, a chronic decrease in HR and improvement in baroreflex sensitivity. The effect of sympathectomy on BP was counteracted by increased vascular sensitivity to catecholamines in WKY rats and SHRs and/or by the enhanced secretion of adrenal hormones, which was more pronounced in WKY rats.
- MeSH
- Baroreflex drug effects MeSH
- Blood Vessels drug effects innervation physiopathology MeSH
- Restraint, Physical MeSH
- Guanethidine pharmacology MeSH
- Hypertension physiopathology MeSH
- Cardiovascular Physiological Phenomena drug effects MeSH
- Catecholamines metabolism MeSH
- Blood Pressure drug effects MeSH
- Rats MeSH
- Adrenal Glands growth & development metabolism physiopathology MeSH
- Rats, Inbred SHR MeSH
- Rats, Inbred WKY MeSH
- Stress, Psychological MeSH
- Heart Rate drug effects MeSH
- Sympatholytics pharmacology MeSH
- Vasoconstrictor Agents pharmacology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Existing experimental studies of the effect of sympathetic nerve fibers on bone marrow cells are based on the systemic administration of neurotoxic 6-hydroxydopamine. The method of global chemical sympathectomy has some serious disadvantages and could lead to questionable results. We describe a new method of local chemical sympathectomy of rat femoral bone marrow using guanethidine (Ismelin) delivery using an osmotic mini pump. Local guanethidine treatment for 14days led to complete elimination of sympathetic fibers in femoral bone marrow in contrast to bone marrow of contralateral or naïve femurs. Ablation of sympathetic fibers was associated with a loss of rat endothelial cell marker (RECA) indicating immunophenotype changes in blood vessel endothelial cells, but no significant effect of guanethidine was found on the survival of endothelial cells and mesenchymal stem cells in vitro. Moreover, local guanethidine treatment also elicited a significant reduction of Nestin+/SDF1+ mesenchymal stem cells and c-Kit+/CD90+ hematopoietic stem cells in femoral bone marrow. Tissue-specific chemical sympathectomy of rat bone marrow by guanethidine overcomes some of the drawbacks of systemic administration of neurotoxic compounds like 6-hydroxydopamine and delivers unequivocal evidence on the effects of sympathetic innervation on the cell content of bone marrow.
- MeSH
- Human Umbilical Vein Endothelial Cells drug effects metabolism pathology MeSH
- Femur drug effects innervation metabolism pathology MeSH
- Fluorescent Antibody Technique MeSH
- Guanethidine pharmacology MeSH
- Bone Marrow drug effects innervation metabolism MeSH
- Humans MeSH
- Mesenchymal Stem Cells drug effects metabolism pathology MeSH
- Models, Animal MeSH
- Rats, Wistar MeSH
- Flow Cytometry MeSH
- Sympathectomy, Chemical MeSH
- Sympathetic Nervous System drug effects metabolism pathology MeSH
- Sympatholytics pharmacology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- Biomarkers analysis blood MeSH
- Denervation methods statistics & numerical data MeSH
- Animal Experimentation statistics & numerical data MeSH
- Financing, Organized MeSH
- Drug Combinations MeSH
- Guanethidine administration & dosage pharmacology MeSH
- Immunohistochemistry methods statistics & numerical data MeSH
- Capsaicin administration & dosage pharmacology MeSH
- Rats surgery MeSH
- Norepinephrine analysis blood MeSH
- Receptors, Calcitonin Gene-Related Peptide analysis blood MeSH
- Heart drug effects MeSH
- Animals MeSH
- Check Tag
- Rats surgery MeSH
- Animals MeSH
- MeSH
- Adult MeSH
- Pheochromocytoma MeSH
- Guanethidine analogs & derivatives MeSH
- Middle Aged MeSH
- Humans MeSH
- Neuroblastoma MeSH
- Radiopharmaceuticals diagnostic use MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
